title: Extracapsular spread in head and neck carcinoma: impact of site and human papillomavirus status.
abstract: BACKGROUND
  Extracapsular spread (ECS) in cervical lymph node metastases from head and neck squamous cell carcinoma (SCC) is regarded as an adverse prognostic factor and is often used to select patients who may benefit from adjuvant therapy. The prognostic value of ECS was evaluated for patients with oropharyngeal SCC (OPC; with known p16/human papillomavirus [HPV] status) and for patients with SCC of the oral cavity (OCC).
  
  
  METHODS
  Disease-specific survival (DSS) was assessed among SCC patients with cervical lymph node metastases (n = 347, including 133 patients with OPC and 214 patients with OCC). All patients were treated surgically between 1983 and 2009. ECS status was determined by pathologists at the time of initial pathologic evaluation and confirmed for this study. HPV status of patients with OPC was determined via immunohistochemistry for p16 and in situ hybridization.
  
  
  RESULTS
  Among OCC patients, ECS was a significant, independent factor influencing DSS. For OCC patients with ECS, 3-year DSS was 45% (95% confidence interval [CI], 36%-56%); for those without ECS, 3-year DSS was 71% (95% CI, 62%-81%; P = .0018). The effect of ECS was independent of the number of positive lymph nodes as well as other clinical, pathologic, and treatment variables. Of the 133 OPC patients, 76 (57%) were p16-positive and 57 (43%) were p16-negative. ECS status did not correlate with DSS among p16-positive or p16-negative OPC patients.
  
  
  CONCLUSIONS
  ECS was not associated with worse DSS in p16-positive or p16-negative OPC patients. Adverse prognostic value of ECS in OCC patients was confirmed. Cancer 2013;119:3302-8. © 2013 American Cancer Society.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Maxwell
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Diana
authors.initials: D
authors.lastname: Cunningham
authors.forename: Vikas
authors.initials: V
authors.lastname: Mehta
authors.forename: Seungwon
authors.initials: S
authors.lastname: Kim
authors.forename: Eugene N
authors.initials: EN
authors.lastname: Myers
authors.forename: Jonas
authors.initials: J
authors.lastname: Johnson
authors.forename: Simion
authors.initials: S
authors.lastname: Chiosea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D030361:Papillomavirus Infections / Q000473:pathology*; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D055815:Young Adult
keywords: Extracapsular spread; HPV; oral cavity; p16, oropharynx; squamous cell carcinoma